Progressively severe hematologic and pathologic changes in mixed hematopoietic chimeras containing an increasing percentage of HbS.

Histologic images are shown for a representative sample of chimeric mice as follows: lethally irradiated C57BL/6 mouse reconstituted with normal C3H.SW bone marrow (left column), mixed chimeric mouse with 16.8% HbS (19.6% normal myeloid chimerism) generated by lethal irradiation followed by reconstitution with a mixture of transgenic sickle and C3H.SW bone marrow (middle column), and mixed chimeric mouse with 91% HbS (0.2% normal myeloid chimerism) generated by lethal irradiation and reconstitution with only transgenic sickle bone marrow (right column). Mice were humanely killed for histologic analysis 6 months after transplantation. (A-C). Peripheral blood smears demonstrate increasing hypochromia and polychromasia with increasing levels of HbS. Two morphologically distinct populations of RBCs are apparent in the 16.8% sickle chimera, as indicated by arrows in panel B. The 91% sickle chimera, panel C, has nucleated RBCs (dark arrow) and sickle forms (open arrow). (D-I) Sections of spleen are shown at low power (D-F) and high power (G-I). Low power illustrates loss of follicular architecture in mice with a majority of HbS. High power illustrates increasing extramedullary hematopoiesis as well as increasing congestion and hemosiderin deposition in mice with larger proportions of HbS. (J-L) Liver infarcts (arrows) are present in mice with as little as 16.8% HbS in the blood, as well as in mice with a majority of HbS. Magnifications: panels A-C, 160 ×; D-F, 40 ×; G-L, 100 ×.